TY - JOUR
T1 - Association between RCT methodology and disease indication with mineralocorticoid-related toxicity for patients receiving abiraterone acetate for advanced prostate cancer
T2 - A meta-analysis of RCTs
AU - Hall, Mary E.
AU - Padgett, Whitney J.
AU - Klaassen, Zachary
AU - Magee, Diana E.
AU - Luckenbaugh, Amy N.
AU - Laviana, Aaron A.
AU - Satkunasivam, Raj
AU - Schaffer, Kerry
AU - Wallis, Christopher J.D.
N1 - Copyright © 2023 Elsevier Inc. All rights reserved.
PY - 2023/10
Y1 - 2023/10
N2 - INTRODUCTION: While abiraterone acetate (AA) has demonstrated survival benefit in advanced prostate cancer (APC), meaningful cardiotoxicity is observed. It is unclear whether the magnitude differs based on disease indication and concurrent steroid administration.METHODS: We performed a systematic review and meta-analysis of phase II/III RCTs of AA in APC published as of August 11, 2020. Primary outcomes examined were all- and high-grade (grade ≥ 3) hypokalemia and fluid retention, and secondary outcomes included hypertension and cardiac events. We performed random effects meta-analysis comparing intervention (AA + steroid) and control (placebo ± steroid), stratified by treatment indication and whether patients received steroids.RESULTS: Among 2,739 abstracts, we included 6 relevant studies encompassing 5901 patients. Hypokalemia and fluid retention were observed more frequently among patients receiving AA (odds ratio [OR] 3.10 [95% CI 1.69-5.67] and 1.41 [95% CI 1.19-1.66]). This was modified by whether patients in the control received steroids: trials where control patients did not demonstrated a larger association between AA and hypokalemia (OR 6.88 [95% CI 1.48-2.36] versus OR 1.86 [95% CI 4.97-9.54], P < .0001) and hypertension (OR 2.53 [95% CI 1.91-3.36] vs. OR 1.55 [95% CI 1.17-2.04], P = .1) than those where steroids were administered. We observed heterogeneity due to indication: there were greater effects on hypokalemia (P < 0001), hypertension (P = .03), and cardiac disorders (P = .01) among patients treated for mHSPC than mCRPC.CONCLUSIONS: The magnitude of cardiotoxicity with AA differs based on trial design and disease indication. These data are valuable in treatment decisions and highlight utilization of appropriate data for counseling.
AB - INTRODUCTION: While abiraterone acetate (AA) has demonstrated survival benefit in advanced prostate cancer (APC), meaningful cardiotoxicity is observed. It is unclear whether the magnitude differs based on disease indication and concurrent steroid administration.METHODS: We performed a systematic review and meta-analysis of phase II/III RCTs of AA in APC published as of August 11, 2020. Primary outcomes examined were all- and high-grade (grade ≥ 3) hypokalemia and fluid retention, and secondary outcomes included hypertension and cardiac events. We performed random effects meta-analysis comparing intervention (AA + steroid) and control (placebo ± steroid), stratified by treatment indication and whether patients received steroids.RESULTS: Among 2,739 abstracts, we included 6 relevant studies encompassing 5901 patients. Hypokalemia and fluid retention were observed more frequently among patients receiving AA (odds ratio [OR] 3.10 [95% CI 1.69-5.67] and 1.41 [95% CI 1.19-1.66]). This was modified by whether patients in the control received steroids: trials where control patients did not demonstrated a larger association between AA and hypokalemia (OR 6.88 [95% CI 1.48-2.36] versus OR 1.86 [95% CI 4.97-9.54], P < .0001) and hypertension (OR 2.53 [95% CI 1.91-3.36] vs. OR 1.55 [95% CI 1.17-2.04], P = .1) than those where steroids were administered. We observed heterogeneity due to indication: there were greater effects on hypokalemia (P < 0001), hypertension (P = .03), and cardiac disorders (P = .01) among patients treated for mHSPC than mCRPC.CONCLUSIONS: The magnitude of cardiotoxicity with AA differs based on trial design and disease indication. These data are valuable in treatment decisions and highlight utilization of appropriate data for counseling.
KW - Abiraterone
KW - Antiandrogen
KW - Cardiotoxicity
KW - Metastatic prostate cancer
KW - Prostate Cancer
KW - Hypertension
KW - Prednisone/therapeutic use
KW - Humans
KW - Male
KW - Treatment Outcome
KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects
KW - Hypokalemia/chemically induced
KW - Randomized Controlled Trials as Topic
KW - Mineralocorticoids/therapeutic use
KW - Cardiotoxicity/etiology
KW - Abiraterone Acetate/adverse effects
KW - Prostatic Neoplasms, Castration-Resistant/drug therapy
UR - http://www.scopus.com/inward/record.url?scp=85160266071&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85160266071&partnerID=8YFLogxK
U2 - 10.1016/j.clgc.2023.04.007
DO - 10.1016/j.clgc.2023.04.007
M3 - Review article
C2 - 37236862
AN - SCOPUS:85160266071
SN - 1558-7673
VL - 21
SP - e370-e377
JO - Clinical Genitourinary Cancer
JF - Clinical Genitourinary Cancer
IS - 5
ER -